Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Abstract

BACKGROUND:The authors previously observed that enhancer of zeste homolog 2 (EZH2) overexpression was associated significantly with the development of oral cancer. In the current study, they investigated whether EZH2 can function as a prognostic predictor for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Expression levels of EZH2 in HNSCC cells were detected using reverse transcriptase-polymerase chain reaction (PCR) and Western blot analyses. In addition, the effects of EZH2 ablation on the proliferation and invasion of HNSCC cells were investigated through small interfering RNA (siRNA)-mediated knockdown. Real-time PCR and immunohistochemistry were used to evaluate EZH2 and cyclin D1 expression in 46 HNSCC samples, and the expression levels also were re-evaluated in 124 independent samples by immunohistochemistry. RESULTS: EZH2 expression was elevated remarkably in HNSCC specimens and cell lines. Upon EZH2 silencing, the proliferation and invasion of HNSCC cells were remarkably suppressed. EZH2 expression frequently was correlated with cyclin D1 expression (P ¼ .034) and tumor differentiation (P ¼ .020). In addition, both EZH2 messenger RNA levels and EZH2 protein levels were strongly associated with signs of histologic severity (P ¼ .012 and P ¼ .032, respectively). Univariate analysis revealed that high EZH2 expression was associated with worse overall survival (P ¼ .001) and disease-free survival (P ¼ .002). The combined expression of EZH2 and cyclin D1 had superior prognostic ability for patients with HNSCC than the expression of either marker alone. In multivariate analysis, EZH2 expression was identified as an independent predictor of overall and disease-free survival. CONCLUSIONS: The current results indicated that EZH2 is an independent prognostic indicator for patients with HNSCC. In addition, an analysis of the combined expression of EZH2 and cyclin D1 can serve as a more powerful prognostic predictor for patients with HNSCC. Cancer 2012;118:2858-71.

Prognostic significance of histone methyltransferase enhancer of zeste homolog 2 in patients with cervical squamous cell carcinoma

“…In this study, immunohistochemical staining was applied to determine EZH2 expression status in a cohort of patients with CSCC and the association of EZH2 expression and clinical outcome of these patients. EZH2 staining was found exclusively in nuclei as shown in previous studies (13,28). Furthermore, for the first time, these findings showed that the aberrant overexpression of EZH2 correlates with the poor survival rates of patients with CSCC (Fig.…”

Galangin inhibits growth of human head and neck squamous carcinoma cells in vitro and in vivo

“…Upon phosphorylation, pRb releases the transcription factor E2F, which is then able to activate the transcription of genes required for G1/S phase transition [32]. It has been reported that cyclin D1 is overexpressed in many human cancers including HNSCC, and it is associated with enhanced tumor growth, chemotherapy resistance and poor prognosis [33][34][35]. Thus, suppression of cyclin D1 may be a useful target for the therapy of HNSCC.…”

TGM3, a candidate tumor suppressor gene, contributes to human head and neck cancer

“…As previously described [44], the human head and neck squamous cell carcinoma cell lines WSU-HN4, HN6, HN12, HN13 and HN30 (kindly provided by the University of Maryland Dental School, USA) and CAL-27 (American Type Culture Collection, ATCC, USA) were cultured in Dulbecco’s modified Eagle medium (DMEM; GIBCO-BRL, USA) supplemented with 10% heat-inactivated FBS (GIBCO-BRL), penicillin (100 units/ml), and streptomycin (100 μg/ml) at 37°C in a humidified 5% CO2 atmosphere. SCC-4, SCC-9 and SCC-25 cells (purchased from the ATCC) were cultured in DMEM/F12 medium (GIBCO-BRL) supplemented with 10% heat-inactivated FBS, penicillin (100 units/ml), and streptomycin (100 μg/ml).…”